Hybrid Molecular Imaging of ER in Breast Cancer Patients With DCIS

Phase 2

Completed

Conditions: Breast Cancer
Ductal Carcinoma in Situ - Category

Interventions: Drug: (18F)FES
Drug: Gadobenate dimeglumine

Registration Number: NCT03703492

Lead Sponsor: University of Wisconsin, Madison

Brief Summary: This prospective, one-arm study which will enroll participants with biopsy-proven DCIS scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care. Eligible participants will be consented for participation in the research study which includes a directed breast PET/MRI with 18F-FES. 18F-FES uptake of the known malignancy will be measured on the PET/MRI examination using standardized uptake values (SUV) and tumor-to-normal tissue ratios.

Detailed Description: Integrated whole-body magnetic resonance imaging (MRI)-positron emission tomography (PET) scanners have recently been introduced for clinical use. This technology combines the anatomic and perfusion data obtained with Dynamic Contrast Enhanced (DCE) MRI with functional imaging data obtained from PET. For breast imaging, the combination of MRI and PET has important potential to improve diagnostic accuracy and provide molecular characterization of breast cancer. The overall purpose of this research is to determine the technical feasibility of simultaneous breast DCE MRI with 18F-FES PET for measuring estrogen receptor (ER) in patients with ductal carcinoma in situ (DCIS) and identifying patients with low-risk of disease recurrence. The hypothesis is that quantitative 18F-FES uptake parameters from PET/MRI will correlate well with the ER immunohistochemistry score and with low-risk recurrence scores.

Primary Objective 1) To compare quantitative 18F-FES uptake of biopsy-proven DCIS measured using PET/MRI with ER protein levels determined by immunohistochemistry.

Secondary Objectives

1. To determine the optimal cut-point 18F-FES uptake value for distinguishing between ER+ and ER-negative DCIS

2. To determine the test-retest reproducibility of quantitative assessment of tumor 18F-FES uptake

3. To determine the optimal cut-point 18F-FES uptake value for distinguishing between low-risk DCIS and intermediate/high-risk DCIS

4. To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100)

5. To measure the upgrade rate to invasive cancer at surgical excision

6. To correlate tumor 18F-FES uptake with serum estradiol and sex hormone binding globulin levels.

Exploratory Objective

1) To correlate tumor cell density with 18F-FES uptake on PET/MRI

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 12

Inclusion Criteria

Diagnosis of biopsy-proven DCIS without invasion or microinvasion measuring at least 1.0 cm in diameter by any imaging modality
Undergoing diagnostic breast MRI ordered by the referring clinician for staging and extent of disease

Exclusion Criteria

Inability or unwillingness to provide informed consent to the study
Surgery, radiation, neoadjuvant chemo/endocrine therapy for the current malignancy prior to study enrollment
Participants currently taking or have taken an ER-blocking medication (e.g. tamoxifen, raloxifene) within 6 weeks prior to study enrollment
Pregnant or lactating women
Participant with intolerance or contraindications for MRI or gadolinium-based contrast agents
Participant girth exceeds the bore of the MRI/PET scanner
Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FES
Participants in liver failure as judged by the patient's physician, due to the hepatobiliary clearance of 18F-FES
Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be allowed to participate as long as the following criteria are met:
- The participant has their own prescription for the medication
- The informed consent process is conducted prior to the self-administration of this medication
- They come to the research visit with a driver or an alternative plan for transportation (e.g. Uber, taxi, etc.)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Research Arm	Gadobenate dimeglumine	Directed breast PET/MRI with 18F-FES; 18F-FES uptake of the known malignancy to be measured on the PET/MRI examination
Research Arm	(18F)FES	Directed breast PET/MRI with 18F-FES; 18F-FES uptake of the known malignancy to be measured on the PET/MRI examination

Primary Outcome Measures

Name	Time	Method
18F-FES Uptake in DCIS	1 day	18F-FES uptake of biopsy-proven ductal carcinoma in situ (DCIS) measured using PET/MRI will be reported in Standardized Uptake Values (SUV).

Secondary Outcome Measures

Name	Time	Method
Serum Estradiol Levels	1 day	Mean serum estradiol levels will be reported to summarize the outcome measure.
Prognostic Risk Categories Determined Using Van Nuys Prognostic Index, the MSKCC Nomogram	2 months	ROC curve analysis will be performed to determine the optimal cut-point for 18F-FES SUVmax to distinguish low-risk DCIS and intermediate/high-risk DCIS. Risk categories will be determined using the Van Nuys Prognostic Index, the Memorial Sloan-Kettering Cancer Center Nomogram, and the research-based Oncotype DX DCIS score. Sensitivity and specificity will be determined with two-sided 95% confidence intervals. The area under the curve (AUCs) for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the 18F-FES uptake value with the maximum sensitivity and specificity. This analysis will be done separately for each risk assessment model.
Research-based Oncotype DX DCIS Scores	12 months	To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100), scatter plots of continuous quantitative 18F-FES uptake (SUVmax) on the y-axis and research-based Oncotype DX DCIS scores (unitless) on the x-axis will be created to explore the distribution of the measurements. Pearson's or Spearman's rank correlation will be used to evaluate the association between quantitative 18F-FES uptake and research-based Oncotype DX DCIS score. The correlation coefficient (rho) and 95% confidence interval will be reported.
Number of Participants With Invasive Cancer at Surgical Excision	2 months	This percentage will be calculated by dividing the number of patients with invasive breast cancer diagnosed at the time of surgical excision by the number of patients with percutaneous biopsy-proven DCIS in the study.
Serum Sex Hormone Binding Globulin Levels	1 day	A correlation analysis of sex hormone binding globulin levels will be performed using Pearson's or Spearman's rank correlation. Scatter plots, correlation coefficients (rho) and 95% confidence intervals will be reported.